PUBLICATION
Insights into structure and dynamics of extracellular domain of Toll-like receptor 5 in Cirrhinus mrigala (mrigala): A molecular dynamics simulation approach
- Authors
- Rout, A.K., Acharya, V., Maharana, D., Dehury, B., Udgata, S.R., Jena, R., Behera, B., Parida, P.K., Behera, B.K.
- ID
- ZDB-PUB-210115-4
- Date
- 2021
- Source
- PLoS One 16: e0245358 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Molecular Dynamics Simulation
- Fish Proteins/chemistry
- Fish Proteins/metabolism*
- Toll-Like Receptor 5/chemistry
- Toll-Like Receptor 5/metabolism*
- Protein Domains
- Animals
- Carps/metabolism*
- Flagellin/metabolism*
- Zebrafish
- Salmonella/metabolism*
- Amino Acid Sequence
- Protein Binding
- PubMed
- 33444377 Full text @ PLoS One
Citation
Rout, A.K., Acharya, V., Maharana, D., Dehury, B., Udgata, S.R., Jena, R., Behera, B., Parida, P.K., Behera, B.K. (2021) Insights into structure and dynamics of extracellular domain of Toll-like receptor 5 in Cirrhinus mrigala (mrigala): A molecular dynamics simulation approach. PLoS One. 16:e0245358.
Abstract
The toll-like receptor 5 (TLR5) is the most conserved important pattern recognition receptors (PRRs) often stimulated by bacterial flagellins and plays a major role in the first-line defense against invading pathogenic bacteria and in immune homeostasis. Experimental crystallographic studies have shown that the extracellular domain (ECD) of TLR5 recognizes flagellin of bacteria and functions as a homodimer in model organism zebrafish. However, no structural information is available on TLR5 functionality in the major carp Cirrhinus mrigala (mrigala) and its interaction with bacterial flagellins. Therefore, the present study was undertaken to unravel the structural basis of TLR5-flagellin recognition in mrigala using structural homodimeric TLR5-flagellin complex of zebrafish as reference. Integrative structural modeling and molecular dynamics simulations were employed to explore the structural and mechanistic details of TLR5 recognition. Results from structural snapshots of MD simulation revealed that TLR5 consistently formed close interactions with the three helices of the D1 domain in flagellin on its lateral side mediated by several conserved amino acids. Results from the intermolecular contact analysis perfectly substantiate with the findings of per residue-free energy decomposition analysis. The differential recognition mediated by flagellin to TLR5 in mrigala involves charged residues at the interface of binding as compared to the zebrafish complex. Overall our results shows TLR5 of mrigala involved in innate immunity specifically recognized a conserved site on flagellin which advocates the scientific community to explore host-specific differences in receptor activation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping